Virulence genes in a probioticE. oliproduct with a recorded long history of safe use

Abstract

The probiotic product Symbioflor2 (DSM 17252) is a bacterial concentrate of six different Escherichia coli genotypes, whose complete genome sequences are compared here, between each other as well as to other E. coli genomes. The genome sequences of Symbioflor2 E. coli components contained a number of virulence-associated genes. Their presence seems to be in conflict with a recorded history of safe use, and with the observed low frequency of adverse effects over a period of more than 6 years. The genome sequences were used to identify unique sequences for each component, for which strain-specific hybridization probes were designed. A colonization study was conducted whereby five volunteers were exposed to an exceptionally high single dose. The results showed that the probiotic E. coli could be detected for 3 months or longer in their stools, and this was in particular the case for those components containing higher numbers of virulence-associated genes. Adverse effects from this long-term colonization were absent. Thus, the presence of the identified virulence genes does not result in a pathogenic phenotype in the genetic background of these probiotic E. coli.

Evaluating the Safety of Potential Probiotic Enterococcus durans KLDS6.0930 Using Whole Genome Sequencing and Oral Toxicity Study

“…Thus, it applies to secreted proteins, cell surface structures, and hydrolytic enzymes that contribute not only to bacterial pathogenicity but also to adhesion and protection (Wassenaar et al, 2015). Remarkably, many probiotic-related traits could be associated to virulence factors; therefore, in silico analyses must be considered in the appropriate context.…”

A Review of Research Conducted with Probiotic E. coli Marketed as Symbioflor

“…The finding that there were a number of virulence genes present in the genomes of probiotic Symbioflor, as outlined by Wassenaar and colleagues [33], was no longer a surprise, as by now there was ample evidence that virulence genes are not exclusively found in pathogenic bacteria. The results of the volunteer study were also incorporated in this paper, as well as a ten-year long collation of all side effects collected from commercial use [33].…”

“…The results of the volunteer study were also incorporated in this paper, as well as a ten-year long collation of all side effects collected from commercial use [33]. In view of the large number of sold doses, this list of collected side effects was surprisingly short.…”

Campylobacter jejuni Increases Flagellar Expression and Adhesion of Noninvasive Escherichia coli: Effects on Enterocytic Toll-Like Receptor 4 and CXCL-8 Expression

“…Furthermore, G. duodenalis was shown to restore virulence in attenuated mutants of Citrobacter rodentium in C. elegans infection models (84). Researchers have reported the presence of virulence genes in probiotic E. coli (Symbioflor2; DSM 17252) despite the absence of adverse effects during long-term commercial use (85), but these findings were based on only five healthy volunteers. Disease-inciting consequences of commensal/ probiotic E. coli have been documented; administration of the probiotic E. coli Nissle 1917, which was given in response to gastroenteritis induced by a coinfection of rotavirus and adenovirus, resulted in severe sepsis in a preterm infant (86).…”